We propose to develop the x-ray Wolter capillary mirror with outstanding optical properties that will impact many existing x-ray characterization and analysis tools relevant to biomedical research. In combination with recently available high brightness microfocus x-ray sources, it could increase the throughput of many x-ray techniques up to 10 times and reduce initial tool purchase cost and subsequent maintenance cost. For the proposing company, we plan to use it in our x-ray 3D imaging systems with sub-30 nm resolution, including a prototype 3D imaging system developed under a NIH phase II funding, which is optimized for imaging biological samples at 30nm resolution. The combination of this performance improvement and lower cost will help to make the tool widely deployed in biological laboratories. 3D x-ray imaging of cells, cell clusters and tissues at 30nm resolution has the potential to open new insights into the organization, evolution and connectivity of biological systems and naturally complements the already available toolset for biological researchers. The Wolter capillary mirror will also substantially improve the performance of many other well established, relevant x-ray techniques, including protein crystallography for determination of crystallographic structures of proteins and viruses, and small angle scattering for studying biological macromolecules in native solution both in vitro and in vivo, which are important tools for drug development and the understanding of disease. Similar to that for x-ray microscopy, a throughput gain of 10X may be expected for some specific applications in these other x-ray techniques. During the phase II project, we plan to refine our fabrication processes and improve our metrology capability to allow the fabrication of Wolter capillary lenses with a point spread function better than 1 <m. Project Narrative Successful development of the proposed Wolter mirror optic will make 3-D x-ray microscopy for biological applications more powerful, affordable, and practical by reducing image acquisition times from several hours to tens of minutes (approximately 10X throughput gain). Exciting capabilities include in-situ 3D imaging of cell and tissue specimens with 30 nm resolution that have undergone little morphological and functional change from their natural living state. In addition to 3-D x-ray imaging other x-ray techniques, such as x-ray diffraction and small angle scattering, critical to drug discovery and understanding of disease, can expect a similar throughput increase from this development. [unreadable] [unreadable] [unreadable]